Prescribing information

 

Durable relapse-free survival at five years1

TAFINLAR (dabrafenib) and MEKINIST (trametinib), the first and only targeted therapy to show DURABLE five-year relapse-free survival vs. placebo in adult BRAF V600-positive patients with completely resected Stage III melanoma1,2

 

Key Clinical Data Insights

The efficacy and safety of TAFINLAR + MEKINIST for the adjuvant treatment of adult patients with BRAF V600-positive completely resected Stage III melanoma has been studied in a large Phase III trial, COMBI-AD.3

Please visit the COMBI-AD safety page for further information on the TAFINLAR + MEKINIST safety profile in the adjuvant setting.

 

 

DURABLE relapse-free survival (RFS) at five years was seen in 52% of patients with TAFINLAR + MEKINIST and the reduced risk of relapse or death vs. placebo was 49%.1,2

The median RFS time for the TAFINLAR + MEKINIST arm was not reached at the cut-off due to a low event rate, whereas the median RFS time for the placebo arm (95% CI) was 16.6 months (12.7, 22.1).1,2

The COMBI-AD trial showed that patients treated with TAFINLAR and MEKINIST had a 45% reduction in the risk of developing distant metastases or dying compared to placebo (five-year distant metastasis-free survival 65% vs. 54%).1,2

TAFINLAR + MEKINIST is the only oral adjuvant therapy with three-year overall survival data (86% of patients are alive at three years with treatment). Final overall survival analysis will be performed when 299 overall survival events have occurred.3

COMBI-AD was a randomised, double-blind, placebo-controlled, Phase III trial that compared TAFINLAR + MEKINIST vs. placebo in adult patients with Stage III BRAF V600E/K-positive melanoma.3 The planned duration of treatment was 12 months.3

 

Image of flowchart showing Trial design for COMBI-AD

COMBI-AD trial showed a 49% reduction in risk of relapse or death after median follow-up of five years with TAFINLAR + MEKINIST vs. placebo1,2

 

  • Five-year relapse-free survival (RFS) was 52% in the TAFLINAR + MEKINIST arm vs. 36% in the placebo arm (HR: 0.51, 95% CI: 0.42, 0.61).1,2
  • The median RFS time for the TAFINLAR + MEKINIST arm was not reached at the cut-off due to low event rate, whereas the median RFS time for the placebo arm (95% CI) was 16.6 months (12.7, 22.1).1,2

Relapse-free survival rates at five years1-3

 

Image of graph detailing relapse-free survival rates at five years1,2

TAFINLAR + MEKINIST at five years reduced the risk of developing distant metastases or dying by 45% vs. placebo1,2

 

Distant metastasis-free survival at five years†1,2,4

 

Image of graph detailing distant metastasis-free survival at five years†1,2

86% of patients treated with TAFINLAR + MEKINIST were alive at three years vs. 77% of patients receiving placebo in the COMBI-AD (P=0.0006, non-significant)*3

 

Overall survival for patients at three years3

 

Image of graph detailing overall survival for patients at three years3

*These results did not meet the prespecified conservative interim boundary of P=0.0000193

No overall survival (OS) analysis was conducted at five years due to predefined group sequential testing scheme. The final OS analysis will be performed when 299 OS events have occurred.

A post-hoc subgroup analysis of RFS based on AJCC 8 demonstrated a consistent clinical benefit favouring TAFINLAR + MEKINIST compared with placebo1,2

 

Relapse-free survival in subgroups: AJCC 81,2

 

 
 

TAFINLAR + MEKINIST did not negatively impact quality of life during treatment or during four years of follow-up5

 

  • Health-Related Quality of Life (HRQoL) assessment using the EuroQoL EQ-5D-3L questionnaire (utility score) and visual analogue scale (VAS) was an exploratory endpoint.5
  • Patients reporting HRQoL during 12 months of treatment with TAFINLAR+MEKINIST, and during four years of follow-up, showed no clinically meaningful changes from baseline in either arm, during treatment or afterwards.5
  • Importantly, patients who experienced the most common adverse events (AEs) associated with TAFINLAR + MEKINIST did not have a clinically meaningful decrease in exploratory VAS scores from baseline, and HRQoL improved over time.5
  • QoL decreased in both treatment arms upon disease recurrence, demonstrating the value of remaining recurrence free.5

The risk of needing subsequent anti-cancer therapy following treatment with TAFINLAR + MEKINIST was lower than with placebo1,2

 

There were 173 (40%) patients in the TAFINLAR + MEKINIST treatment arm and 232 (54%) patients in the placebo arm taking subsequent anti-cancer therapy during the five-year follow-up period.2

Post treatment anti-cancer therapy during five-year follow-up period2

 

Image of table detailing post treatment anti-cancer therapy during five-year follow-up period2

References

  1. Dummer R, et al. N Engl J Med 2020; DOI: 10.1056/NEJMoa2005493.
  2. Hauschild A, et al. Presented at ASCO 2020 virtual congress, 29–31 May, Chicago, USA.
  3. Long GV, et al. N Engl J Med 2017;377:1813–1823.
  4. Hauschild A, et al. J Clin Oncol 2018;36:3441–3449.
  5. Schadendorf D, et al. Presented at ASCO 2018;1–5 June, Chicago, USA.
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UK | December 2020 | 100880
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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis via [email protected]rtis.com or online through the pharmacovigilance intake (PVI) tool at www.report.novartis.com
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